1. Field of the Invention
This invention relates to antimicrobial substances, and in particular, relates to compositions effective in inhibiting sexually transmitted bacteria, such as gonococci.
2. Description of the Related Art
Genital tract infections caused by pathogens such as the gonococci (Neisseria gonorrhoeae) and other sexually transmitted diseases (STDs) are difficult to cure once the infection has occurred, and it is difficult to prevent the spread of such infections particularly by sexual transmission. A wide variety of products have been developed to treat infections due to sexually transmitted bacteria, such as gonococci, including ampicillin, procaine penicillin G and ceftriaxone.
Many of the therapeutic agents once used to treat sexually transmitted bacterial infections have become decreasingly effective as the bacteria have developed increased chromosomally-mediated and plasmid-mediated resistance. For example, certain penicillin-resistant strains of N. gonorrhoeae have achieved epidemic proportions in certain parts of the United States.
Some compounds with general antibacterial activity, such as benzalkonium chloride and chlorhexidine digluconate, are also known to have spermicidal activity. Nonoxynol-9, a spermicidal contraceptive, is known to have some antiviral and antibacterial activity. Generally, however, the compositions and devices, that have been developed as contraceptives, including oral contraceptives, spermicides, and barrier methods and devices such as condoms, diaphragms and contraceptive sponges, do not possess potent activity in inhibiting microorganisms that cause STDs. Although the proper use of some contraceptive devices such as condoms provides a barrier to the further spread of STDs, condoms do not provide a means for inhibiting bacterial activity once an infection has occurred.
Nonoxynol-9, and other polyethoxyethanol compounds have been widely used as spermicides. Recently, D-propranolol and related compounds with beta-adrenergic blocking activity have been incorporated into the nonoxynol compositions, to decrease the tissue irritation caused by the nonoxynol itself. U.S. Pat. No. 4,795,761. When propranolol was incorporated into the nonoxynol-9 composition to decrease the tissue irritation, a surprising synergistic effect on spermicidal activity was noted; however, the D-propranolol by itself was found to have reduced spermicidal activity as compared to the nonoxynol-9 by itself, or to the combination of the two components. Propranolol was not known to have antibacterial activity nor to inhibit STD microorganisms such as N. gonorrhoeae prior to this study. The above-cited patent and all other patents and publications cited herein are hereby incorporated by reference.
DL-propranolol has also been found to inhibit motility of spermatozoa (Peterson and Freund, Biol. of Repro. 13: 552-556, 1975) and undissolved propranolol tablets (Inderal.TM.) were found to have potential as a vaginally applied contraceptive (Zipper et al., Brit. Med. J. 287: 1245-1246, 1983).
Because of the inhibitory effect of propranolol on sperm motility, the inhibitory activity of propranolol on protozoan flagellar activity and growth has been investigated. D-propranolol at about 10-3 moles/liter in a tissue culture medium inhibited motility and growth of Giardia lamblia and Trichomonas vaginalis (Farthing et al., J. Antimicrobial Chemotherapy 20: 519-522, 1987).
Although propranolol has spermicidal characteristics, it is much less potent as a spermicide than nonoxynol-9. Data published by Chijioke et al. (Contraception 34: 207-211, 1986) demonstrate that nonoxynol-9 is about four times more potent in vitro as a spermicide than D-propranolol. Similar in vitro results obtained by P. M. Saling (unpublished, Final Report entitled "Spermicidal Effect of D-propranolol," January, 987), showed that semen samples treated with several concentrations of nonoxynol-9 always had a lower percentage of motile sperm than those treated with the respective concentrations of D-propranolol.
It is therefore an object of this invention to provide a method of treatment with a composition that is inhibitory to sexually transmitted bacteria.
It is a further object of this invention to provide a method for inhibiting sexually transmitted bacteria that also is capable of providing contraceptive protection.
Other objects and advantages will be more fully apparent from the following discharge and appended claims.